"We desperately need new treatment options for patients with liver cancer, the second leading cause of cancer deaths worldwide," said Richard Kim, M.D., Moffitt Cancer Center, an investigator for the study. "Unlike many other tumor types, there are no biomarker-driven targeted therapies currently approved for HCC, the most common form of liver cancer. These preliminary data are exciting as they suggest BLU-554 may offer the first targeted therapy in a biomarker-defined group of patients with advanced HCC. I am excited to evaluate BLU-554 in the expansion portion of the Phase 1 clinical trial, where we are prospectively selecting patients for FGFR4 pathway activation."

"We are very encouraged to see early anti-tumor activity in patients with confirmed FGF19 overexpression and consistent evidence of FGFR4 pathway modulation during the dose escalation part of this first-in-human clinical trial," said Andy Boral, M.D., Chief Medical Officer of Blueprint Medicines. "Now that we have demonstrated proof-of-concept, determined the maximum tolerated dose (MTD), and implemented FGF19 biomarker screening globally, we can move rapidly to enroll patients in the expansion part of the study to more fully evaluate the activity of BLU-554 in patients with advanced HCC."

Data from the Ongoing Global Phase 1 Clinical Trial

BLU-554 was evaluated in the dose escalation stage of a Phase 1 clinical trial in patients with advanced HCC. As of the data cutoff date of November 7, 2016, 25 patients had been treated in the dose escalation portion of the Phase 1 clinical trial at five dose levels (ranging from 140 mg once daily (QD) to 900 mg QD), with the majority of patients having previously received sorafenib. The study was designed to retroactively assess patient biopsies for FGFR4 pathway activation after enrollment by evaluating levels of FGF19, the protein that activates FGFR4, using an investigational immunohistochemistry (IHC) assay. Prospective screening of patients with the investigational IHC assay was implemented during dose escalation, enabling enrollment of enrichment patients with confirmed FGF19 overexpression which resulted in a larger number than anticipated of biomarker positive patients being enrolled. Blueprint Medicines has initiated the expansion portion of the Phase 1 clinical trial, and enrollment is ongoing.

Pharmacokinetic (PK) data across all dose levels showed rapid oral absorption, a mean half-life of approximately ten hours, and exposure in the expected therapeutic range based on HCC xenograft models.